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Confidence and psychosis: a neuro-computational account of contingency learning disruption by NMDA blockade.

Fabien Vinckier, Raphaël Gaillard, S Palminteri, L Rigoux, Alexandre Salvador, A Fornito, R Adapa, M O Krebs, M Pessiglione, P C Fletcher

Molecular Psychiatry June 9, 2015 DOI: 10.1038/mp.2015.73 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Placebo-controlled, double-blind, crossover functional MRI study Peer reviewed
Population Healthy volunteers
Intervention Ketamine
Topics Ketamine
Keywords Humans Psychoses, substance-induced Receptors, n-methyl-d-aspartate Magnetic resonance imaging Bayes theorem Double-blind method Learning Conditioning, classical Psychotic disorders Adult Female
Key points Bayesian model comparison indicated that in an unstable environment reinforcement learning parameters are downregulated depending on confidence level, an adaptive mechanism the authors report was specifically disrupted by ketamine. Drug effects were underpinned by altered neural activity in a fronto-parietal network reflecting the confidence-based shift to exploitation of learned contingencies. The authors suggest an early characteristic of psychosis lies in persistent doubt that undermines stabilization of behavioral policy, resulting in failure to exploit regularities in the environment.

Abstract

A state of pathological uncertainty about environmental regularities might represent a key step in the pathway to psychotic illness. Early psychosis can be investigated in healthy volunteers under ketamine, an NMDA receptor antagonist. Here, we explored the effects of ketamine on contingency learning using a placebo-controlled, double-blind, crossover design. During functional magnetic resonance imaging, participants performed an instrumental learning task, in which cue-outcome contingencies were probabilistic and reversed between blocks. Bayesian model comparison indicated that in such an unstable environment, reinforcement learning parameters are downregulated depending on confidence level, an adaptive mechanism that was specifically disrupted by ketamine administration. Drug effects were underpinned by altered neural activity in a fronto-parietal network, which reflected the confidence-based shift to exploitation of learned contingencies. Our findings suggest that an early characteristic of psychosis lies in a persistent doubt that undermines the stabilization of behavioral policy resulting in a failure to exploit regularities in the environment.

Comparable studies

Other randomized controlled trials on ketamine, most cited first.

Study Year Design Participants
Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community 1994 Randomized controlled trial n = 19
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery 2005 Randomized controlled trial n = 75
Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures 2014 Randomized controlled trial n = 41
Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers 2000 Single-blind placebo-controlled study n = 20

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